ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.100G>A (p.Gly34Ser) (rs387907306)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000624509 SCV000741801 pathogenic Inborn genetic diseases 2016-09-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Baylor-Hopkins Center for Mendelian Genomics,Johns Hopkins University RCV000030819 SCV000266520 pathogenic Shprintzen-Goldberg syndrome criteria provided, single submitter research
GeneDx RCV000200686 SCV000250672 pathogenic not provided 2014-12-11 criteria provided, single submitter clinical testing p.Gly34Ser (GGC>AGC): c.100 G>A in exon 1 of the SKI gene (NM_003036.3) The G34S mutation in the SKI gene has been reported in three individuals with clinical diagnoses of SGS (Doyle et al., 2012; Carmignac et al., 2012, Schepers et al., 2014). The Gly34 residue appears to be a recurrent mutation hotspot in the R-SMAD binding domain of the SKI gene, as different mutations impacting this amino acid (G34D, G34C, G34V) have been reported (Doyle et al., 2012; Carmignac et al., 2012, Schepers et al., 2014). Mutations in nearby residues (S31L, L32V, L32P, P35S, P35Q) have also been reported in association with SGS, further supporting the functional importance of this region of the protein. G34S results in a non-conservative amino acid substitution of Glycine at a position that is conserved, when present, across species. This variant was found in TAADV2-1,SKI
OMIM RCV000030819 SCV000053494 pathogenic Shprintzen-Goldberg syndrome 2015-02-01 no assertion criteria provided literature only
SIB Swiss Institute of Bioinformatics RCV000030819 SCV000803523 likely pathogenic Shprintzen-Goldberg syndrome 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Likely Pathogenic, for Shprintzen-Goldberg craniosynostosis syndrome, in Autosomal Dominant manner. The following ACMG Tag(s) were applied: PM5 => Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM1 => Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation. PM6 => Assumed de novo, but without confirmation of paternity and maternity (PMID:24736733). PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS4-Moderate => PS4 downgraded in strength to Moderate (PMID:23023332,23103230,24736733).

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